! PROJECT SUMMARY In 2015, evidence that e-cigarette use (?vaping?) in adolescents and young adults (AYAs) had increased and was associated with increased risk of cigarette smoking initiation generated concern in the public health community. Subsequent research has left the field with several critical questions, including: (1) whether vaping truly has a causal effect on smoking or merely reflects a common liability toward deviancy among ?high-risk? AYAs with emotional or behavioral problems, (2) whether an emerging wave of new vaping products, including new nicotine products such as JUUL, and an increasingly diverse class of products dedicated to vaping cannabis plant, oils, and waxes, may increase the appeal and addictive potential of vaping, and (3) whether there exist particular characteristics of vaping products and biopsychosocial mechanisms that underlie the risk of AYA vaping initiation, progression, and transition to other forms of drug use that could be targeted in prevention efforts. The uncertainties regarding the impact of AYA vaping have left policy officials with little evidence to determine if AYA vaping should be prioritized in public health programs, and if so, the most effective strategies for prevention. To address the evidence needs and provide a flexible framework for future study of the impact of various vaping products on the AYA tobacco product and cannabis use burden, we will test a novel ?catalyst model? of AYA vaping. The catalyst model proposes two steps, which we will evaluate in Aims 1 and 2 of this proposal. Step 1 (AIM 1). To determine whether (a) AYAs with fewer emotional-behavioral risk factors who have been previously deterred from drug use in traditional (non-vaporized) forms are at risk of vaping initiation, (b) the unique qualities and product features of vaping (e.g., concealability, flavors, appealing technology, social acceptability, low perceived harm) increase risk of AYA vaping, and (c) features of vaping products disproportionately increase the risk of vaping initiation for low-risk AYAs. Step 2 (AIM 2). To determine whether (a) vaping increases the risk of cross-product transitions involving initiation of other vaping products, or combustible nicotine or cannabis, as well as increases risk of progression to problematic drug use outcomes, including dependence, poly-drug use, and chronic drug use through early adulthood, (b) rewarding effects from exposure to nicotine, cannabinoids, and other product components (e.g. flavorings) increases risk of cross-product transitions and problematic drug use outcomes, and (c) product characteristics modify this association. To test the model, we will leverage data collected from participants from age 14-19 (2013-2018) from our existing cohort and follow participants into early adulthood (20-23, from 2019-2023; N~2000). We will also recruit a new cohort of 9th grade students at age 14 (N=2500) at the same schools as part of a cohort-sequential design that will apply causal inference analytic approaches to determine whether observed associations are likely causal. Collectively, this project will provide critical information regarding the priority and potential targets of public health efforts aimed at reducing the potential adverse public health effects resulting from AYA vaping, including tobacco-related cancer.